Molecular Photoacoustic Imaging using Multitargeted Contrast Agents

使用多靶点造影剂的分子光声成像

• 批准号: 8528387
• 负责人: Carolyn Louise Bayer
• 金额: $ 5.66万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528387
• 关键词: Anatomy; Animal Model; Biocompatible Materials; Biological; Biopsy; Cancer Biology; Cancerous; Cell model; Cell physiology; Cells; Characteristics; Collaborations; Communication; Complex; Contrast Media; Correlation Studies; Development; Diagnostic Imaging; Disease; Disease Progression; Early Diagnosis; Endocytosis; Enrollment; Epidermal Growth Factor Receptor; Ethics; Fellowship; Gel; Generations; Goals; Gold; Human; Image; Imaging Techniques; In Vitro; Injection of therapeutic agent; Integrins; Knowledge; Lasers; Longitudinal Studies; Malignant Neoplasms; Mammary Neoplasms; Measures; Medical Imaging; Mentors; Mentorship; Methods; Modeling; Molecular; Monitor; Mus; Optics; Patients; Pharmaceutical Preparations; Physiology; Property; Regulation; Research; Research Personnel; Resolution; Signal Transduction; Staging; System; Technical Expertise; Therapeutic Effect; Tissues; Training; Tyrosine Kinase Inhibitor; Ultrasonography; Variant; Water; absorption; angiogenesis; animal tissue; cellular targeting; chromophore; computerized data processing; design; imaging modality; improved; in vivo; lapatinib; malignant breast neoplasm; molecular imaging; molecular scale; molecular/cellular imaging; nanoparticle; nanorod; neoplastic cell; optical imaging; photoacoustic imaging; plasmonics; receptor; receptor expression; response; skills; small molecule; treatment planning; tumor; tumor growth; tumor xenograft; uptake

DESCRIPTION (provided by applicant): The proposed research seeks to use integrated photoacoustic imaging and ultrasound, combined with molecularly targeted contrast agents, to acquire non-invasive in vivo molecular images of tumor cell receptor expression. While methods of molecular imaging have been developed, challenges with spatial resolution, depth of field, temporal resolution and sensitivity remain. Multimodal photoacoustic and ultrasound imaging combines advantageous features of optical and ultrasound imaging, enabling optical probing of contrast at a high resolution at a depth of several centimeters in vivo. The proposed research seeks to demonstrate photoacoustic molecular imaging of tumor receptor expression. The hypothesis is that photoacoustic imaging with multiplex targeted contrast agents, combined with high resolution ultrasound imaging, will provide the necessary sensitivity and resolution to detect and distinguish between regions of in vivo tumors which are expressing different receptors. The first aim of the project is to demonstrate in vitro photoacoustic imaging of multiplex targeted contrast agents which have been endocytosed in cells expressing the relevant receptor. Inclusions containing targeted cells will then be injected in ex vivo animal tissue and imaged using multispectral photoacoustics in order to develop statistical correlations to distinguish between contrast agents with varying optical properties, and native tissue chromophores. The second aim will demonstrate in vivo photoacoustic and ultrasound imaging of complex tumor receptor expression within cancer tumor xenografts in murine animal models using injections of the multiplex targeted contrast agents. The third aim will perform longitudinal studies on tumor growth and response to drug treatment within the murine model, using the combined photoacoustic and ultrasound imaging techniques to image targeted contrast agents uptaken within the tumor. The training plan proposed to accomplish these goals has been designed to establish trainee mentors with specific technical expertise. The selected mentors are experts in ultrasound and photoacoustic imaging; the synthesis and applications of plasmonic nanoparticles for biomedical applications; and the cell expression and regulation of cancer; respectively. The PI will enroll in formal training in the ethical conduct of research and in training specific to her research field, to prepare her for independent research.

描述（由申请人提供）：拟议的研究试图使用集成的光声成像和超声检查，并结合了分子靶向对比剂，以获取肿瘤细胞受体表达的无创的体内分子图像。尽管已经开发出分子成像的方法，但仍存在空间分辨率，景深，时间分辨率和灵敏度的挑战。多模式光声和超声成像结合了光学和超声成像的有利特征，从而在体内数厘米的深度高分辨率下以高分辨率的对比度进行光学探测。拟议的研究旨在证明肿瘤受体表达的光声分子成像。假设是，具有多重靶向对比剂的光声成像，结合高分辨率超声成像，将提供必要的灵敏度和分辨率，以检测和区分表达不同受体的体内肿瘤区域。该项目的第一个目的是证明多重靶向对比剂的体外光声成像，这些对比剂已在表达相关受体的细胞中被内吞作用。然后将含有靶向细胞的夹杂物注入离体动物组织中，并使用多光谱光声学成像，以开发统计相关性，以区分具有不同光学特性的对比剂和天然组织染色体。第二个目的将证明使用多重靶向对比剂的注射鼠类动物模型中癌症肿瘤异种移植物中复杂肿瘤受体表达的体内光声和超声成像。第三个目标将使用鼠模型中的肿瘤生长和对药物治疗的反应进行纵向研究，并使用光声和超声成像技术与图像靶向的对比剂在肿瘤中捕获的图像。旨在实现这些目标的培训计划旨在建立具有特定技术专业知识的学员导师。选定的导师是超声和光声成像的专家。等离子纳米颗粒在生物医学应用中的合成和应用；以及癌症的细胞表达和调节；分别。 PI将参加研究和研究领域的培训的正式培训，以便她为独立研究做好准备。